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EP4067051B1 - Biotinten-versorgungssystem und verfahren zum dreidimensionalen biodrucken damit - Google Patents

Biotinten-versorgungssystem und verfahren zum dreidimensionalen biodrucken damit Download PDF

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Publication number
EP4067051B1
EP4067051B1 EP19954555.9A EP19954555A EP4067051B1 EP 4067051 B1 EP4067051 B1 EP 4067051B1 EP 19954555 A EP19954555 A EP 19954555A EP 4067051 B1 EP4067051 B1 EP 4067051B1
Authority
EP
European Patent Office
Prior art keywords
bioink
hydrogel
syringe
storage part
temperature
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP19954555.9A
Other languages
English (en)
French (fr)
Other versions
EP4067051A4 (de
EP4067051C0 (de
EP4067051A1 (de
Inventor
Geun Seon Ahn
Min Kyung Kim
Kyung Hyun Min
In Gyu Lee
Dong Won Seok
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
T&R Biofab Co Ltd
Original Assignee
T&R Biofab Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020190153493A external-priority patent/KR102189959B1/ko
Priority claimed from KR1020190153502A external-priority patent/KR102253727B1/ko
Application filed by T&R Biofab Co Ltd filed Critical T&R Biofab Co Ltd
Publication of EP4067051A1 publication Critical patent/EP4067051A1/de
Publication of EP4067051A4 publication Critical patent/EP4067051A4/de
Application granted granted Critical
Publication of EP4067051C0 publication Critical patent/EP4067051C0/de
Publication of EP4067051B1 publication Critical patent/EP4067051B1/de
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/04—Enzymes or microbial cells immobilised on or in an organic carrier entrapped within the carrier, e.g. gel or hollow fibres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10—Processes of additive manufacturing
    • B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/205—Means for applying layers
    • B29C64/209—Heads; Nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/255—Enclosures for the building material, e.g. powder containers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/307—Handling of material to be used in additive manufacturing
    • B29C64/314—Preparation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/307—Handling of material to be used in additive manufacturing
    • B29C64/321—Feeding
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/307—Handling of material to be used in additive manufacturing
    • B29C64/321—Feeding
    • B29C64/336—Feeding of two or more materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/386—Data acquisition or data processing for additive manufacturing
    • B29C64/393—Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00—Processes of additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y40/00—Auxiliary operations or equipment, e.g. for material handling
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y40/00—Auxiliary operations or equipment, e.g. for material handling
    • B33Y40/10—Pre-treatment
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y50/00—Data acquisition or data processing for additive manufacturing
    • B33Y50/02—Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/14—Scaffolds; Matrices
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y70/00—Materials specially adapted for additive manufacturing

Definitions

  • the present disclosure relates to generally to a bioink supply system. More particularly, the present disclosure relates to a bioink supply system capable of continuously supplying bioink by mixing a hydrogel and cells in real time during a three-dimensional (3D) bioprinting process, and to a 3D bioprinting method using the same.
  • the present disclosure relates generally to a 3D print head. More particularly, the present disclosure relates to a 3D print head capable of preventing dew condensation from occurring on a low-temperature head by improving thermal insulation performance of a high-temperature head, and to a 3D printer having the same.
  • a bioprinting composition used in 3D bioprinting is a 3D printing material including cells, growth factors, etc. on the basis of a hydrogel, etc.
  • the 3D bioprinting environment is maintained in a sterile state, and temperature and humidity are maintained constant.
  • a clean 3D bioprinting environment can be created by disposing a 3D bioprinter in a clean room, but this is costly and requires special authentication facilities.
  • a stagnant area occurs due to the flow of air (airflow), and contaminants such as fine particles are collected in the stagnant area, causing a printing result to be physically or biologically contaminated.
  • Another objective of the present disclosure is to provide a 3D print head having a cover made of a polymer material with very low thermal conductivity so as to exhibit excellent thermal insulation performance, thereby preventing dew condensation from occurring on a 3D print head operated at a low temperature, and to provide a 3D printer and a 3D printing system having the same.
  • the hydrogel storage part (1100) may include a pH adjusting means, and the cell storage part (1200) may include a stirring means.
  • the mixing part (1300) may include an impeller as a mixing means (1310), and the sensor part (1500) may include a laser sensor or a stretch sensor (1510).
  • a three-dimensional bioprinting method including: storing a hydrogel in a hydrogel storage part (1100); storing a cell solution containing live cells in a cell storage part (1200); supplying the hydrogel and the cell solution from the hydrogel storage part (1100) and the cell storage part (1200) to a mixing part (1300); mixing the hydrogel and the cell solution in the mixing part (1300) and supplying the mixture to a syringe (1400); and maintaining a constant level of bioink inside the syringe (1400) by operating or stopping a pump (1320) for supplying the bioink to the syringe (1400) and wherein the storing of the cell solution is performed under conditions of CO 2 concentration of 5%, temperature of 37°C, and pH of 7 to 7.5.
  • the hydrogel may include alginate, fibrinogen, carboxymethyl cellulose, heparan sulfate, hyaluronic acid, collagen, or dextran.
  • a three-dimensional (3D) print head including: a syringe (100) accommodating a printing composition (1) therein and jetting the printing composition (1) through a nozzle (150) at a lower portion thereof; a heating block (120) formed on an outer peripheral surface of the syringe (100); and a cover (130) formed to surround the heating block.
  • the printing composition (1) may include a thermoplastic polymer, and the cover (130) may be an engineering plastic or a ceramic material having excellent thermal insulation and heat resistance properties.
  • a multi-3D print head including: the above-described 3D print head as a high-temperature head (160); and as a low-temperature head (170), a syringe (101) accommodating a hydrogel therein and jetting the hydrogel through a nozzle at a lower portion thereof.
  • a moisture absorber (141) may be further provided on an outer peripheral surface of the syringe (101) constituting the low-temperature head (170).
  • the moisture absorber (141) may include a wool or cotton material having excellent absorbency, or silica gel, calcium chloride, or zeolite.
  • the moisture absorber (141) may be detachably attached to the outer peripheral surface of the syringe (101) by means of a magnet, Velcro, or bolt fastening.
  • a multi-head 3D printer including: a high-temperature head (160) including a syringe (100) accommodating a printing composition (1) therein and jetting the printing composition (1) through a nozzle (150) at a lower portion thereof, a heating block (120) formed on an outer peripheral surface of the syringe (100), and a cover (130) formed to surround the heating block; and a low-temperature head (170) including a syringe (101) accommodating a hydrogel therein and jetting the hydrogel through a nozzle at a lower portion thereof, and a moisture absorber (141) attached to an outer peripheral surface of the syringe (101), in which heat may be transferred to the inside of the syringe (100) through the heating block (120), and the heat may be blocked from being emitted to the outside by the cover (130).
  • a high-temperature head including a syringe (100) accommodating a printing composition (1) therein and jetting the printing composition (1) through a
  • the present disclosure may further include a 3D bioprinting system for three-dimensionally printing a biotissue using the multi-head 3D printer described above.
  • a clean bench system including: a housing; an air supply unit supplying air into the housing; a driving device located inside the housing; and an airflow guide formed to cover the driving device to control an airflow of supplied air.
  • the driving device may be at least one selected from the group consisting of a 3D printer, a stirring device, an incubator, and an automatic pipette device accompanied by mechanical operation or movement.
  • a plurality of surfaces constituting the airflow guide may form an angle of equal to or less than 90 degrees with the direction of the airflow of supplied air, and may guide the direction of the supplied airflow from the air supply unit downwards, thereby removing a stagnant area of the airflow.
  • the housing may be provided with a transparent window so that the inside of the housing can be viewable from the outside.
  • a high efficiency particulate air filter HEPA filter
  • a pre-filter may be used as the filter.
  • a clean bench system driving method including: a temperature and humidity control step of supplying air whose temperature and humidity are adjusted by a temperature and humidity adjustment unit to an air supply unit; an air supply step of filtering the air supplied to the air supply unit with a filter and supplying the filtered air into a housing; and an air discharging step of discharging the air supplied to the inside of the housing through a vent formed in a lower portion of the housing.
  • An airflow of the air supplied through the air supply unit may be controlled by an airflow guide formed to cover a driving device located inside the housing.
  • the cover according to the present disclosure can suppress heat inside the 3D print head from being emitted to the outside, so it is possible to lower the power consumption for maintaining a constant temperature inside the 3D print head.
  • the present disclosure relates to a 3D print head for accommodating or jetting a printing composition, among components of a 3D printer.
  • the present disclosure relates to a head structure capable of effectively preventing dew condensation from occurring on the surface of a multi-3D print head operated in different temperature ranges, and to a 3D printer having the same, and to a 3D printing system.
  • a description of other components of the 3D printer unnecessary in describing the present disclosure will be omitted herein.
  • the high-temperature head 160 for the 3D printer includes: a syringe 100 for jetting a printing composition 1; a heating block 120 formed on an outer peripheral surface of the syringe 100; and a cover 130 formed to surround the heating block 120.
  • the high-temperature head 160 for the 3D printer according to the present disclosure may jet the printing composition 1 while being moved by a driving device and a control device of the 3D printer.
  • the heating block 120 is preferably formed on the outer peripheral surface of the syringe 100 so as to evenly transfer heat to the printing composition 1 accommodated in the syringe 100.
  • the heating block 120 is heated by receiving heat from a cartridge heater mounted on a rear surface thereof, and is preferably made of an aluminum material having excellent thermal conductivity.
  • the cartridge heater may include a heating wire, a thermocouple element, or a Peltier element.
  • the cover 130 blocks the heat generated by the heating block 120 from being transferred to the outside, thereby preventing dew condensation from occurring in another 3D print head operated at a relatively low temperature, and is preferably made of a material having very low thermal conductivity and excellent heat resistance that can withstand high temperatures.
  • the cover 130 may include: a main cover 131 accommodating the heating block 120 therein; an upper cover 132 coupled to an upper end of the main cover 131 to surround an upper end of the heating block 120; and a lower cover 133 coupled to a lower end of the main cover 131 to surround a lower end of the heating block 120.
  • a main cover 131 accommodating the heating block 120 therein
  • an upper cover 132 coupled to an upper end of the main cover 131 to surround an upper end of the heating block 120
  • a lower cover 133 coupled to a lower end of the main cover 131 to surround a lower end of the heating block 120.
  • the upper cover 132 may include a first coupling hole 134 formed in an outer surface of the upper cover 132 and a first through-hole 135 formed in the center of the upper cover 132 and through which the syringe 100 passes.
  • the main cover 131 and the upper cover 132 may be coupled to each other by means of screw coupling through the first coupling hole 134, or may be coupled to each other by means of an adhesive such as an epoxy resin that can be used at a high temperature.
  • the lower cover 133 may include a second coupling hole 136 formed in an outer surface of the lower cover 133 and a second through-hole 137 formed in the center of the lower cover 133 and through which the syringe 100 passes.
  • the main cover 131 and the lower cover 133 may be coupled to each other by means of screw coupling through the second coupling hole 136, or may be coupled to each other by means of an adhesive such as a resin that can be used at a high temperature.
  • screw coupling it is preferable to use a screw made of the same material as the cover 130 in order to maximize a thermal insulation effect.
  • the thickness of the cover 130 is not particularly limited, but is preferably in the range of 1 to 10 mm, and it is advantageous in terms of thermal insulation performance when the thickness is larger than at least 1 mm. However, when considering a precise movement of the head, a thickness exceeding 10 mm is not preferable because it may deteriorate precision of a printed material.
  • the cover 130 may further include a nozzle cover 138 extending from the lower cover 133 and formed between the heating block 120 and the nozzle 150.
  • the nozzle cover 138 blocks heat of the nozzle 150 from being transmitted to the outside to maintain a constant temperature inside the nozzle 150, and prevents dew condensation from occurring in the nozzle 150.
  • the main cover 131, the upper cover 132, the lower cover 133, and the nozzle cover 138, which constitute the cover 130, may be configured, if necessary, in the form of a hollow structure having an empty space therein to utilize an air layer with an excellent thermal insulation effect.
  • a multi-3D print head may include a low-temperature head 170 illustrated in FIG. 5 together with the high-temperature head 160.
  • the low-temperature head 170 for 3D printing includes a syringe 101 accommodating a hydrogel therein and jetting the hydrogel through a nozzle at a lower portion thereof, and may further include a moisture absorber 141 capable of absorbing dew condensation occurring on the surface of the head.
  • the moisture absorber 141 may be formed in a form in which a hygroscopic material is coated on the outer peripheral surface of the syringe 101 of the low temperature head 130 or is detachably attached thereto, and absorbs dew condensation to prevent it from falling onto a printed material being 3D printed.
  • the multi-3D print head according to the present disclosure may include both the high-temperature head 160 and the low-temperature head 170 simultaneously, and can be effectively applied to a 3D printer and a 3D printing system having such a multi-head structure. Also, it is possible to effectively prevent the occurrence of dew condensation caused by a temperature difference between each head and to minimize the contamination of a final 3D structure. Thus, the present disclosure is more useful in a 3D bioprinting system for 3D printing of biotissue.
  • FIG. 7 is a perspective view illustrating a clean bench system according to another embodiment of the present disclosure.
  • FIG. 8 is a view illustrating the inside of the clean bench system according to the other embodiment of the present disclosure.
  • the clean bench system includes: a housing 310; an air supply unit 320 formed on the housing 310 and supplying air into the housing 310; a 3D printer 330 serving as a driving device provided inside the housing 310; an airflow guide 340 formed to cover the 3D printer 330; and a vent 313 formed in a lower portion of the housing 310.
  • the housing 310 provides a clean area in a clean bench, and may accommodate a driving device such as the 3D printer 330 therein.
  • a driving device such as the 3D printer 330
  • the 3D printer has been described as an example of the driving device, any driving mechanism that has mechanical movement within the clean bench may be included without any particular limitation. Examples include various experimental devices such as a 3D printer, an automatic pipette device, a stirrer, and an incubator, and more preferably, a 3D printer capable of precisely controlling the shape and structure of a printing result.
  • the housing 310 may be made of various metal materials such as steel, stainless steel, aluminum, titanium, etc.
  • the shape of the housing 310 is not particularly limited as long as it has a shape that can surround the driving device.
  • the shape of the housing 310 may be a cylinder, a cube, or a cuboid.
  • a transparent window 311 through which the inside of the housing 310 is viewable from the outside may be formed.
  • the 3D printer 330 serving as the driving device installed inside the housing 310, may be checked, or the operating state of the 3D printer 330 may be checked.
  • the transparent window 311 may be made of a transparent material such as glass or plastic.
  • the air supply unit 320 supplies air into the housing 310, and is formed on the housing 310.
  • the air supplied through the air supply unit 320 is discharged to the outside of the housing 310 through the vent 313 formed in the lower portion of the housing 310.
  • the clean bench system guides the flow of air in one direction (i.e., in a vertical direction from top to bottom of the housing) to cross the 3D printer 330 serving as the driving device.
  • the air supply unit 320 includes a suction port 325 sucking air from the outside of the housing 310, a supply port 321 supplying the sucked air from the suction port 325 into the housing 310; and a filter 323 installed in the supply port 321.
  • a high efficiency particulate air filter (HEPA filter) or a pre-filter may be used, preferably a HEPA filter class EU10 having an efficiency of 95% to 99.9%, and more preferably a HEPA filter class U17 having an efficiency of 99.999995%.
  • the 3D printer 330 which is a representative driving device, may be provided inside the housing 310, which is a space in which a clean environment is maintained, and may be formed integrally with the housing 310 or may be formed separately from the housing 310 to be detachably attached thereto.
  • the 3D printer 300 may include: a print head 3 jetting a printing composition 1; a support plate 200 on which the jetted printing composition 1 is stacked; a head moving unit 4 moving the print head 3; and a stage 5 guiding movement of the head moving unit 4.
  • the print head 3 jets the printing composition 1 while being moved along the stage 5 by the head moving unit 4 to print a 3D structure.
  • the printing composition 1 may be jetted from the print head 3 to the support plate 200 by means of pneumatic pressure.
  • a jet amount and jet speed of the printing composition 1 to be jetted may be adjusted by appropriately controlling the pneumatic pressure according to the concentration of the printing composition 1 and the diameter of a nozzle of the print head 3.
  • the printing composition 1 may include a thermoplastic polymer, a hydrogel, or a mixture thereof, and may further include cells in addition to the thermoplastic polymer or hydrogel if necessary.
  • the thermoplastic polymer may include, but is not limited to, for example, at least one selected from the group consisting of lactide, caprolactone, glycolide, dioxanone, propylene, ethylene, vinyl chloride, butadiene, methyl methacrylate, acrylic acid, 2-2-hydroxyethyl methacrylate, carbonate, and polyethylene terephthalate.
  • the hydrogel may include at least one selected from the group consisting of alginate, fibrinogen, carboxymethyl cellulose, heparan sulfate, hyaluronic acid, collagen, and dextran.
  • FIG. 10 is a perspective view illustrating the airflow guide 340 coupled to the 3D printer 330, according to the other embodiment of the present disclosure.
  • FIG. 11 is a rear view illustrating the airflow guide coupled to the 3D printer 330 according to the other embodiment of the present disclosure.
  • the airflow guide 340 prevents a backflow of air inside the housing 310 caused by the 3D printer 330 and controls an airflow, which is a flow of air supplied to the outside of the 3D printer 330 serving as the driving device, through the air supply unit 320, and is preferably formed in a structure that covers the 3D printer 330.
  • the airflow guide 340 is formed to cover a print head 3 and a head moving unit 4 of the 3D printer 330, and if necessary, may further include a stage cover 343 covering a stage 5 of the 3D printer 330 or a cable cover 345 covering a cable of the 3D printer 330.
  • the cable cover 345 may be formed to slide through a rail structure or the like in conjunction with forward and backward movement of the airflow guide 340 (see FIG. 11 ).
  • surfaces constituting the airflow guide 340 may be formed to form an angle of equal to or less than 90 degrees with an inflow direction of airflow, and it is preferable that angles between the respective surfaces the and the airflow (P1, P2, P3, and P4 are illustrated in the drawings as examples, but are not limited thereto) are all equal to or less than 90° in a downward direction.
  • the surfaces constituting the airflow guide 340 are all inclines surfaces not horizontal surfaces, and the angles (P1, P2, and P3 in FIG. 12 ) between the airflow and the respective inclined surfaces are all equal to or less than 90°. Even more preferably, the angles between the airflow and the inclined surfaces are all less than 90°.
  • the angles may be set in the range of about 40° to 45°.
  • the airflow which is a flow of air supplied from an upper portion of the housing 310 through the air supply unit 320, can be effectively guided in the direction of the vent 313 formed in the lower portion of the housing 310, and fine particles inside the housing 310 can be effectively prevented from stagnating in a certain area to form a stagnant area.
  • the structure and shape of the airflow guide 340 surrounding the 3D printer, which is the driving device, has been mainly described, but the driving device is not limited to the 3D printer.
  • the airflow guide 340 may be fixed in the clean bench to cover the driving device, and if necessary, the airflow guide 340 may be moved by an auxiliary means such as a rail.
  • a separate UV light source may be provided inside the housing 310. Because UV rays has a sterilizing power, the separate UV light source may be provided inside the housing 310 to irradiate an external region of the airflow guide 340 surrounding the 3D printer with UV rays, whereby the operation of the driving device (e.g., a 3D printing process) may be performed in an aseptic environment.
  • the UV light source is preferably formed at a lower end of the air supply unit 320 so that the entire inner region of the housing 310 is evenly irradiated with UV rays.
  • the clean bench system may further include a temperature and humidity adjustment unit 350 supplying air whose temperature and humidity are adjusted to the air supply unit 320.
  • the temperature and humidity adjustment unit 350 includes: a casing 351 having an inlet 353 for allowing air to be introduced therethrough and an outlet 355 for allowing air to be discharged therethrough; a temperature control means provided inside the casing 351 to cool or heat air inside the casing 351; and a humidity control means provided inside the casing 351 to dehumidify or humidify the inside of the casing 351.
  • the inlet 353 is connected to the vent 313 of the housing 310 so that air discharged from the housing 310 is introduced into the temperature and humidity adjustment unit 350, and the outlet 355 is connected to the suction port 325 of the air supply unit 320 so that the air whose temperature and humidity are adjusted is supplied into the housing 310.

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Claims (8)

  1. Biotinten-Versorgungssystem für ein 3D-Drucksystem mit:
    einem Hydrogelspeicherteil (1100);
    einem Zellspeicherteil (1200);
    einem Mischteil (1300), das dazu eingerichtet ist, ein Hydrogel und eine Zelllösung aus dem Hydrogelspeicherteil (1100) und dem Zellspeicherteil (1200) aufzunehmen und zu mischen;
    dadurch gekennzeichnet, dass das Biotinten-Versorgungssystem ferner aufweist:
    ein Sensorteil (1500), das dazu eingerichtet ist, einen Füllstand der Biotinte innerhalb einer Spritze (1400) zu messen; und
    eine Steuergerät (1600), die dazu eingerichtet ist, ein Signal von dem Sensorteil (1500) zu empfangen und einen konstanten Füllstand der Biotinte innerhalb der Spritze (1400) durch Betätigen oder Anhalten einer Pumpe (1320) zur Versorgung der Spritze (1400) mit Biotinte aufrechtzuerhalten, wobei das Mischteil (1300) die durch Mischen des Hydrogels und der Zelllösung hergestellte Biotinte der Spritze (1400) zuführt;
    wobei das Zellspeicherteil (1200) unter Bedingungen einer CO2-Konzentration von 5%, einer Temperatur von 37°C und einem pH-Wert von 7 bis 7,5 gehalten wird.
  2. Biotinten-Versorgungssystem nach Anspruch 1, wobei das Hydrogelspeicherteil (1100) eine pH-Einstelleinrichtung aufweist.
  3. Biotinten-Versorgungssystem nach Anspruch 1, wobei das Zellspeicherteil (1200) eine Rühreinrichtung aufweist.
  4. Biotinten-Versorgungssystem nach Anspruch 1, wobei das Mischteil (1300) einen Impeller als Mischeinrichtung (1310) aufweist.
  5. Biotinten-Versorgungssystem nach Anspruch 1, wobei das Sensorteil (1500) einen Lasersensor oder einen Dehnungssensor (1510) aufweist.
  6. Dreidimensionales Biodruckverfahren, das die nachfolgenden Schritte aufweist:
    Speichern eines Hydrogels in einem Hydrogelspeicherteil (1100);
    Speichern einer Zelllösung, die lebende Zellen enthält, in einem Zellspeicherteil (1200);
    Zuführen des Hydrogels und der Zelllösung von dem Hydrogelspeicherteil (1100) und dem Zellspeicherteil (1200) zu einem Mischteil (1300);
    Mischen des Hydrogels und der Zelllösung in dem Mischteil (1300) und Zuführen der Mischung zu einer Spritze (1400); und
    dadurch gekennzeichnet, dass das Verfahren ferner die nachfolgenden Schritte aufweist:
    Aufrechterhalten eines konstanten Füllstands der Biotinte innerhalb der Spritze durch Betätigen oder Anhalten einer Zuführeinrichtung zum Zuführen der Biotinte zu der Spritze (1400) durch Betätigen oder Anhalten einer Pumpe (1320) zur Versorgung der Spritze (1400) mit Biotinte;
    wobei die Speicherung der Zelllösung unter Bedingungen einer CO2-Konzentration von 5%, einer Temperatur von 37°C und einem pH-Wert von 7 bis 7,5 erfolgt.
  7. Dreidimensionales Biodruckverfahren nach Anspruch 6, wobei das Hydrogel Alginat, Fibrinogen, Carboxymethylcellulose, Heparansulfat, Hyaluronsäure, Collagen oder Dextran aufweist.
  8. Dreidimensionales Biodruckverfahren nach Anspruch 6, wobei die Speicherung des Hydrogels unter Bedingungen einer Temperatur von 10°C bis 15°C und einem pH-Wert von 5 bis 6 erfolgt.
EP19954555.9A 2019-11-26 2019-12-13 Biotinten-versorgungssystem und verfahren zum dreidimensionalen biodrucken damit Active EP4067051B1 (de)

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KR1020190153493A KR102189959B1 (ko) 2019-11-26 2019-11-26 멀티 3d 프린팅 헤드 및 이를 포함하는 3d 프린터
KR1020190153502A KR102253727B1 (ko) 2019-11-26 2019-11-26 바이오 클린 벤치 시스템
PCT/KR2019/017653 WO2021107250A1 (ko) 2019-11-26 2019-12-13 바이오 잉크 공급 시스템 및 이를 이용한 삼차원 바이오 프린팅 방법

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JP7352994B2 (ja) 2023-09-29
US20220411779A1 (en) 2022-12-29
WO2021107250A1 (ko) 2021-06-03
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